Novel 1,3,4-heterodiazole analogues: Synthesis and in-vitro antitumor activity

The synthesis of some new heterodiazole and their annulated imidazo[2,1-b]1,3,4-oxa/thiadiazolone 6a–d, 7a–d; 1,3,4-oxa or thiadiazole[3,2-a]pyrimidine diamine 8a–d and 1,3,4-oxa or thiadiazole-3-piperidino-1-propamide 11a,b derivatives have been described. The obtained compounds were evaluated for their in-vitro antitumor activity. A single dose (10 μM) of the test compounds were used in the full National Cancer Institute (NCI) 60 cell lines panel assay. Compounds 6c and 6d displayed appreciable anticancer activity against leukemia, non-small cell lung, CNS and showed moderate activity against colon, melanoma, and breast cancer cells lines. Compound 6c possessed remarkable broad-spectrum antitumor activity which almost 4 fold more active than the known drug 5-FU with GI50, TGI, and LC50 values of 6.0, 17.4, and 55.1 μM, respectively.

Graphical abstractThe manuscript deals with the synthesis of 1,3,4-oxa/thiadiazole and their annelated imidazo[2,1-b]1,3,4-oxa/thiadiazolone derivatives. The obtained compounds were evaluated for their in-vitro antitumor activity.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Series of 1,3,4-oxa or thiadiazole and their cyclized derivatives were prepared. ► The in-vitro evaluations were used in the NCI 60 cell lines panel assay. ► Compounds 6c,d showed appreciable activity against leukemia, non-small cell lung and CNS. ► Compound 6c proved to be the most active member of this study.